The F glycoprotein of respiratory syncytial virus is one of the targets of a protective immune response; however, immunity following natural infection is incomplete and repeated infections occur in spite of high levels of neutralizing antibody. Extracellular virus may infect cells while spread of intracellular virus may occur following cell-to-cell fusion. In order to better understand the requirements of a protective human immune response we have helped to characterize the binding site of human monoclonal antibody to the fusion glycoprotein of RSV. Intersestingly, the human monoclonal antibody , which neutralizes and inhibits fusion of infected cells, did not compete with murine antibodies , indicating that it binds to a unique site on F. This finding is consitent with previous results from this lab that showed that adult sera with high titers of RSV neutralizing antibody, did not block binding of murine anti-F antibodies. Taken together, these data would suggest that the human immune response is directed torward different epitopes than those recognized by the murine system. The absence of antibodies in human sera directed toward sites resposible for neutralization and inhibiton of fusion may partially explain the basis for repeated infections due to RSV. We are responsible for the review of RSV vaccines and immunotherapeutic agents that have been proposed for the prevention and treatment of RSV infection in neonates and infants. The above studies have allowed us to characterize the repertoire of antibodies in polyclonal products and identify or confirm the specificity of monoclonal products. In addition, we have been able to characterize the antibody's abilty to react with RSV in fusion inhibition assays. Studies in the laboratory that help to identify the reasons that RSV is able to escape neutralization and fusion inhibition will provide information for the development of vaccines and antibodies that will protect against all subgroup A and B strains.